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Manipulating circadian rhythm to modulate tau pathology

Alzheimer’s disease (AD) and fronto-temporal dementia (FTD) are associated with altered circadian rhythm and sleep/wake cycles.

Aims

Define the effects of changing light/dark cycles on the development of tau pathology in tau transgenic mice.

The reasons for this are unclear, but disruptions in sleep-wakefulness probably contribute to the development of pathology in a feed forward manner. Our lab’s previous data demonstrate altered sleep-wakefulness patterns in human-tau transgenic mice.

In the current project, we therefore probe the effects of changing light/dark cycles on the development of tau pathology in tau transgenic mice. The light/dark cycle of the mice will be altered for a number of weeks. The mice then undergo surgery to install electroencephalography/electromyography (EEG/EMG) head-mounts. After recovery from surgery, sleep-wake activity will be assessed by analysis of recorded EEG/EMG signals (“polysomnography”; PSG), and cognition tested in a spatial learning and memory task. After completion of the in-life part of the study, brains will be taken for the analysis by immunohistochemistry and plasma samples for the analysis of melatonin.

Students will learn about current theories underlying AD and FTD, tauopathy, sleep/wake physiology and circadian rhythms. Techniques learning include using transgenic mouse lines, surgery, PSG, cognitive testing in mice, immunohistochemistry and radio-immunoassay.

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